Multifunctional ytterbium oxide buffer for perovskite solar cells.

Perovskite solar cells (PSCs) comprise a solid perovskite absorber sandwiched between several layers of different charge-selective materials, ensuring unidirectional current flow and high voltage output of the devices1,2. A 'buffer material' between the electron-selective layer and the metal electrode in p-type/intrinsic/n-type (p-i-n) PSCs (also known as inverted PSCs) enables electrons to flow from the electron-selective layer to the electrode3-5. Furthermore, it acts as a barrier inhibiting the inter-diffusion of harmful species into or degradation products out of the perovskite absorber6-8. Thus far, evaporable organic molecules9,10 and atomic-layer-deposited metal oxides11,12 have been successful, but each has specific imperfections. Here we report a chemically stable and multifunctional buffer material, ytterbium oxide (YbOx), for p-i-n PSCs by scalable thermal evaporation deposition. We used this YbOx buffer in the p-i-n PSCs with a narrow-bandgap perovskite absorber, yielding a certified power conversion efficiency of more than 25%. We also demonstrate the broad applicability of YbOx in enabling highly efficient PSCs from various types of perovskite absorber layer, delivering state-of-the-art efficiencies of 20.1% for the wide-bandgap perovskite absorber and 22.1% for the mid-bandgap perovskite absorber, respectively. Moreover, when subjected to ISOS-L-3 accelerated ageing, encapsulated devices with YbOx exhibit markedly enhanced device stability.

WWC proteins mediate LATS1/2 activation by Hippo kinases and imply a tumor suppression strategy.

YAP and TAZ (YAP/TAZ), two major effectors of the Hippo signaling pathway, are frequently activated in human cancers. The activity of YAP/TAZ is strictly repressed upon phosphorylation by LATS1/2 tumor suppressors. However, it is unclear how LATS1/2 are precisely regulated by upstream factors such as Hippo kinases MST1/2. Here, we show that WWC proteins (WWC1/2/3) directly interact with LATS1/2 and SAV1, and SAV1, in turn, brings in MST1/2 to phosphorylate and activate LATS1/2. Hence, WWC1/2/3 play an organizer role in a signaling module that mediates LATS1/2 activation by MST1/2. Moreover, we have defined a minimum protein interaction interface on WWC1/2/3 that is sufficient to activate LATS1/2 in a robust and specific manner. The corresponding minigene, dubbed as SuperHippo, can effectively suppress tumorigenesis in multiple tumor models. Our study has uncovered a molecular mechanism underlying LATS1/2 regulation and provides a strategy for treating diverse malignancies related to Hippo pathway dysregulation.

Two Hippo signaling modules orchestrate liver size and tumorigenesis.

The Hippo pathway is a central regulator of organ size and tumorigenesis and is commonly depicted as a kinase cascade, with an increasing number of regulatory and adaptor proteins linked to its regulation over recent years. Here, we propose that two Hippo signaling modules, MST1/2-SAV1-WWC1-3 (HPO1) and MAP4K1-7-NF2 (HPO2), together regulate the activity of LATS1/2 kinases and YAP/TAZ transcriptional co-activators. In mouse livers, the genetic inactivation of either HPO1 or HPO2 module results in partial activation of YAP/TAZ, bile duct hyperplasia, and hepatocellular carcinoma (HCC). On the contrary, inactivation of both HPO1 and HPO2 modules results in full activation of YAP/TAZ, rapid development of intrahepatic cholangiocarcinoma (iCCA), and early lethality. Interestingly, HPO1 has a predominant role in regulating organ size. HPO1 inactivation causes a homogenous YAP/TAZ activation and cell proliferation across the whole liver, resulting in a proportional and rapid increase in liver size. Thus, this study has reconstructed the order of the Hippo signaling network and suggests that LATS1/2 and YAP/TAZ activities are finetuned by HPO1 and HPO2 modules to cause different cell fates, organ size changes, and tumorigenesis trajectories.

Proteolytic activation of angiomotin by DDI2 promotes angiogenesis.

The scaffolding protein angiomotin (AMOT) is indispensable for vertebrate embryonic angiogenesis. Here, we report that AMOT undergoes cleavage in the presence of lysophosphatidic acid (LPA), a lipid growth factor also involved in angiogenesis. AMOT cleavage is mediated by aspartic protease DNA damage-inducible 1 homolog 2 (DDI2), and the process is tightly regulated by a signaling axis including neurofibromin 2 (NF2), tankyrase 1/2 (TNKS1/2), and RING finger protein 146 (RNF146), which induce AMOT membrane localization, poly ADP ribosylation, and ubiquitination, respectively. In both zebrafish and mice, the genetic inactivation of AMOT cleavage regulators leads to defective angiogenesis, and the phenotype is rescued by the overexpression of AMOT-CT, a C-terminal AMOT cleavage product. In either physiological or pathological angiogenesis, AMOT-CT is required for vascular expansion, whereas uncleavable AMOT represses this process. Thus, our work uncovers a signaling pathway that regulates angiogenesis by modulating a cleavage-dependent activation of AMOT.

The Promise and Challenges of Inverted Perovskite Solar Cells.

Recently, there has been an extensive focus on inverted perovskite solar cells (PSCs) with a p-i-n architecture due to their attractive advantages, such as exceptional stability, high efficiency, low cost, low-temperature processing, and compatibility with tandem architectures, leading to a surge in their development. Single-junction and perovskite-silicon tandem solar cells (TSCs) with an inverted architecture have achieved certified PCEs of 26.15% and 33.9% respectively, showing great promise for commercial applications. To expedite real-world applications, it is crucial to investigate the key challenges for further performance enhancement. We first introduce representative methods, such as composition engineering, additive engineering, solvent engineering, processing engineering, innovation of charge transporting layers, and interface engineering, for fabricating high-efficiency and stable inverted PSCs. We then delve into the reasons behind the excellent stability of inverted PSCs. Subsequently, we review recent advances in TSCs with inverted PSCs, including perovskite-Si TSCs, all-perovskite TSCs, and perovskite-organic TSCs. To achieve final commercial deployment, we present efforts related to scaling up, harvesting indoor light, economic assessment, and reducing environmental impacts. Lastly, we discuss the potential and challenges of inverted PSCs in the future.

Active metamaterials for realizing odd mass density.

Solids built out of active components have exhibited odd elastic stiffness tensors whose active moduli appear in the antisymmetric part and which give rise to non-Hermitian static and dynamic phenomena. Here, we present a class of active metamaterial featured with an odd mass density tensor whose asymmetric part arises from active and nonconservative forces. The odd mass density is realized using metamaterials with inner resonators connected by asymmetric and programmable feed-forward control on acceleration and active forces along the two perpendicular directions. The active forces produce unbalanced off-diagonal mass density coupling terms, leading to non-Hermiticity. The odd mass is then experimentally validated through a one-dimensional nonsymmetric wave coupling where propagating transverse waves are coupled with longitudinal ones whereas the reverse is forbidden. We reveal that the two-dimensional active metamaterials with the odd mass can perform in either energy-unbroken or energy-broken phases separated by exceptional points along principal directions of the mass density. The odd mass density contributes to the wave anisotropy in the energy-unbroken phase and directional wave energy gain in the energy-broken phase. We also numerically illustrate and experimentally demonstrate the two-dimensional wave propagation phenomena that arise from the odd mass in active solids. Finally, the existence of non-Hermitian skin effect is discussed in which boundaries host an extensive number of localized modes. It is our hope that the emergent concept of the odd mass can open up a new research platform for mechanical non-Hermitian system and pave the ways for developing next-generation wave steering devices.

Rapid production of kilogram-scale graphene nanoribbons with tunable interlayer spacing for an array of renewable energy.

Graphene nanoribbons (GNRs) are widely recognized as intriguing building blocks for high-performance electronics and catalysis owing to their unique width-dependent bandgap and ample lone pair electrons on both sides of GNR, respectively, over the graphene nanosheet counterpart. However, it remains challenging to mass-produce kilogram-scale GNRs to render their practical applications. More importantly, the ability to intercalate nanofillers of interest within GNR enables in-situ large-scale dispersion and retains structural stability and properties of nanofillers for enhanced energy conversion and storage. This, however, has yet to be largely explored. Herein, we report a rapid, low-cost freezing-rolling-capillary compression strategy to yield GNRs at a kilogram scale with tunable interlayer spacing for situating a set of functional nanomaterials for electrochemical energy conversion and storage. Specifically, GNRs are created by sequential freezing, rolling, and capillary compression of large-sized graphene oxide nanosheets in liquid nitrogen, followed by pyrolysis. The interlayer spacing of GNRs can be conveniently regulated by tuning the amount of nanofillers of different dimensions added. As such, heteroatoms; metal single atoms; and 0D, 1D, and 2D nanomaterials can be readily in-situ intercalated into the GNR matrix, producing a rich variety of functional nanofiller-dispersed GNR nanocomposites. They manifest promising performance in electrocatalysis, battery, and supercapacitor due to excellent electronic conductivity, catalytic activity, and structural stability of the resulting GNR nanocomposites. The freezing-rolling-capillary compression strategy is facile, robust, and generalizable. It renders the creation of versatile GNR-derived nanocomposites with adjustable interlay spacing of GNR, thereby underpinning future advances in electronics and clean energy applications.

Integrase-LEDGF/p75 complex triggers the formation of biomolecular condensates that modulate HIV-1 integration efficiency in vitro.

The pre-integration steps of the HIV-1 viral cycle are some of the most valuable targets of recent therapeutic innovations. HIV-1 integrase (IN) displays multiple functions, thanks to its considerable conformational flexibility. Recently, such flexible proteins have been characterized by their ability to form biomolecular condensates as a result of Liquid-Liquid-Phase-Separation (LLPS), allowing them to evolve in a restricted microenvironment within cells called membrane-less organelles (MLO). The LLPS context constitutes a more physiological approach to study the integration of molecular mechanisms performed by intasomes (complexes containing viral DNA, IN, and its cellular cofactor LEDGF/p75). We investigated here if such complexes can form LLPS in vitro and if IN enzymatic activities were affected by this LLPS environment. We observed that the LLPS formed by IN-LEDGF/p75 functional complexes modulate the in vitro IN activities. While the 3'-processing of viral DNA ends was drastically reduced inside LLPS, viral DNA strand transfer was strongly enhanced. These two catalytic IN activities appear thus tightly regulated by the environment encountered by intasomes.

Radioiodine-refractory differentiated thyroid cancer: Molecular mechanisms and therapeutic strategies for radioiodine resistance.

Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is difficult to treat with radioactive iodine because of the absence of the sodium iodide transporter in the basement membrane of thyroid follicular cells for iodine uptake. This is usually due to the mutation or rearrangement of genes and the aberrant activation of signal pathways, which result in abnormal expression of thyroid-specific genes, leading to resistance of differentiated thyroid cancer cells to radioiodine therapy. Therefore, inhibiting the proliferation and growth of RAIR-DTC with multikinase inhibitors and other drugs or restoring its differentiation and then carrying out radioiodine therapy have become the first-line treatment strategies and main research directions. The drugs that regulate these kinases or signaling pathways have been studied in clinical and preclinical settings. In this review, we summarized the major gene mutations, gene rearrangements and abnormal activation of signaling pathways that led to radioiodine resistance of RAIR-DTC, as well as the medicine that have been tested in clinical and preclinical trials.

Surface Engineering Enables Efficient AgBiS2 Quantum Dot Solar Cells.

Surface ligand chemistry is vital to control the synthesis, diminish surface defects, and improve the electronic coupling of quantum dots (QDs) toward emerging applications in optoelectronic devices. Here, we successfully develop highly homogeneous and dispersed AgBiS2 QDs, focus on the control of interdot spacing, and substitute the long-chain ligands with ammonium iodide in solution. This results in improved electronic coupling of AgBiS2 QDs with excellent surface passivation, which greatly facilitates carrier transport within the QD films. Based on the stable AgBiS2 QD dispersion with the optimal ligand state, a homogeneous and densely packed QD film is prepared by a facile one-step coating process, delivering a champion power conversion efficiency of approximately 8% in the QD solar cells with outstanding shelf life stability. The proposed surface engineering strategy holds the potential to become a universal preprocessing step in the realm of high-performance QD optoelectronic devices.

ADAMTS18 deficiency associates extracellular matrix dysfunction with a higher risk of HER2-positive mammary tumorigenesis and metastasis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for about 20% of all breast cancer cases and is correlated with a high relapse rate and poor prognosis. ADAMTS18 is proposed as an important functional tumor suppressor gene involved in multiple malignancies, including breast cancer. It functions as an extracellular matrix (ECM) modifier. However, it remains unclear whether ADAMTS18 affects mammary tumorigenesis and malignant progression through its essential ECM regulatory function. METHODS: To elucidate the role of ADAMTS18 in HER2-positive mammary tumorigenesis and metastasis in vivo, we compared the incidence of mammary tumor and metastasis between Adamts18-knockout (MMTV)-Her2/ErbB2/Neu+ transgenic mice (i.e., Her2t/w/Adamts18-/-) and Adamts18-wildtype (MMTV)-Her2/ErbB2/Neu+ transgenic mice (i.e., Her2t/w/Adamts18+/+). The underlying mechanisms by which ADAMTS18 regulates HER2-positive tumorigenesis and metastasis were investigated by pathology, cell culture, Western blot and immunochemistry. RESULTS: Adamts18 mRNA is mainly expressed in myoepithelial cells of the mammary duct. ADAMTS18 deficiency leads to a significantly increased incidence of mammary tumors and metastasis, as well as mammary hyperplasia in mice, over 30 months of observation. The proliferation, migration and invasion capacities of primary Her2t/w/Adamts18-/- mammary tumor cells are significantly higher than those of primary Her2t/w/Adamts18+/+ mammary tumor cells in vitro. At 30 months of age, the expression levels of laminin (LNα5), fibronectin (FN) and type I collagen (ColI) in the mammary glands of Her2t/w/Adamts18-/- mice are significantly increased, and the activities of integrin-mediated PI3K/AKT, ERK and JNK signaling pathways are enhanced. CONCLUSIONS: ADAMTS18 deficiency leads to alterations in mammary ECM components (e.g., LNα5, FN, ColI), which are associated with a higher risk of HER2-positive mammary tumorigenesis and metastasis.

Aberrant dynamic functional network connectivity in progressive supranuclear palsy.

BACKGROUND: The clinical symptoms of progressive supranuclear palsy (PSP) may be mediated by aberrant dynamic functional network connectivity (dFNC). While earlier research has found altered functional network connections in PSP patients, the majority of those studies have concentrated on static functional connectivity. Nevertheless, in this study, we sought to evaluate the modifications in dynamic characteristics and establish the correlation between these disease-related changes and clinical variables. METHODS: In our study, we conducted a study on 53 PSP patients and 65 normal controls. Initially, we employed a group independent component analysis (ICA) to derive resting-state networks (RSNs), while employing a sliding window correlation approach to produce dFNC matrices. The K-means algorithm was used to cluster these matrices into distinct dynamic states, and then state analysis was subsequently employed to analyze the dFNC and temporal metrics between the two groups. Finally, we made a correlation analysis. RESULTS: PSP patients showed increased connectivity strength between medulla oblongata (MO) and visual network (VN) /cerebellum network (CBN) and decreased connections were found between default mode network (DMN) and VN/CBN, subcortical cortex network (SCN) and CBN. In addition, PSP patients spend less fraction time and shorter dwell time in a diffused state, especially the MO and SCN. Finally, the fraction time and mean dwell time in the distributed connectivity state (state 2) is negatively correlated with duration, bulbar and oculomotor symptoms. DISCUSSION: Our findings were that the altered connectivity was mostly concentrated in the CBN and MO. In addition, PSP patients had different temporal dynamics, which were associated with bulbar and oculomotor symptoms in PSPRS. It suggest that variations in dynamic functional network connectivity properties may represent an essential neurological mechanism in PSP.

NAT10 inhibition promotes ac4C-dependent ferroptosis to counteract sorafenib resistance in nasopharyngeal carcinoma.

Sorafenib, an anticancer drug, has been shown to induce ferroptosis in cancer cells. However, resistance to sorafenib greatly limits its therapeutic efficacy, and the exact mechanism of resistance is not fully understood. This study investigated the role of N-Acetyltransferase 10 (NAT10) in influencing the anticancer activity of sorafenib in nasopharyngeal carcinoma (NPC) and its molecular mechanism. NAT10 expression was significantly upregulated in NPC. Mechanistically, NAT10 promotes proteins of solute carrier family 7 member 11 (SLC7A11) expression through ac4C acetylation, inhibiting sorafenib-induced ferroptosis in NPC cells. The combined application of sorafenib and the NAT10 inhibitor remodelin significantly inhibits SLC7A11 expression and promotes ferroptosis in NPC cells. In vivo knockout of NAT10 inhibited the growth of sorafenib-resistant NPC. Our findings suggest that NAT10 inhibition might be a promising therapeutic approach to enhance the anticancer activity of sorafenib.

MFN2 suppresses the accumulation of lipid droplets and the progression of clear cell renal cell carcinoma.

Dissolving the lipid droplets in tissue section with alcohol during a hematoxylin and eosin (H&E) stain causes the tumor cells to appear like clear soap bubbles under a microscope, which is a key pathological feature of clear cell renal cell carcinoma (ccRCC). Mitochondrial dynamics have been reported to be closely associated with lipid metabolism and tumor development. However, the relationship between mitochondrial dynamics and lipid metabolism reprogramming in ccRCC remains to be further explored. We conducted bioinformatics analysis to identify key genes regulating mitochondrial dynamics differentially expressed between tumor and normal tissues and immunohistochemistry and Western blot to confirm. After the target was identified, we created stable ccRCC cell lines to test the impact of the target gene on mitochondrial morphology, tumorigenesis in culture cells and xenograft models, and profiles of lipid metabolism. It was found that mitofusin 2 (MFN2) was downregulated in ccRCC tissues and associated with poor prognosis in patients with ccRCC. MFN2 suppressed mitochondrial fragmentation, proliferation, migration, and invasion of ccRCC cells and growth of xenograft tumors. Furthermore, MFN2 impacted lipid metabolism and reduced the accumulation of lipid droplets in ccRCC cells. MFN2 suppressed disease progression and improved prognosis for patients with ccRCC possibly by interrupting cellular lipid metabolism and reducing accumulation of lipid droplets.

Bronchoalveolar lavage fluid analysis in patients with checkpoint inhibitor pneumonitis.

BACKGROUND: Checkpoint inhibitor pneumonitis (CIP) is a relatively uncommon but potentially life-threatening immune-related adverse event (irAE). Lung biopsies have not been commonly performed for CIP patients. Bronchoalveolar lavage fluid (BALF) analysis is a useful diagnostic approach for interstitial lung disease. However, BALF features were inconsistent across different studies. METHODS: We retrospectively reviewed the medical records of 154 patients with pathologically confirmed malignancies and suffering from CIPs between July 2018 and December 2022. Patients who had bronchoalveolar lavage (BAL) data available were enrolled in our study. Patient clinical, laboratory, radiological and follow-up data were reviewed and analyzed. RESULTS: The BALF differential cell count and lymphocyte subset analysis were performed for 42 CIP patients. There were 32 males (76.2%). The mean age at diagnosis of CIP was 62.0 ± 10.4 (range: 31-78) years. The median time to onset of CIP was 98.5 days after the start of immunotherapy. There were 18 patients (42.9%) with low-grade CIPs and 24 patients (57.1%) with high-grade CIPs. The mean lymphocyte percentage was 36.7 ± 22.5%. There were 34 (81%) CIP patients with a lymphocytic cellular pattern. The median ratio of CD3+CD4+/CD3+CD8+ lymphocytes was 0.5 (0.3, 1.0). The ratio was less than 1.0 for 31 CIP patients (73.8%). However, there was no significant difference in the BALF features between patients with low-grade CIPs and those with high-grade CIPs. CONCLUSIONS: The CD3+CD8+ lymphocytosis pattern was the main inflammatory profile in the BALF of CIP patients in this cohort. Targeting CD3+CD8+ lymphocytes might be a treatment option for CIPs.

Nitric oxide mediates positive regulation of Nostoc flagelliforme polysaccharide yield via potential S-nitrosylation of G6PDH and UGDH.

Based on our previous findings that salicylic acid and jasmonic acid increased Nostoc flagelliforme polysaccharide yield by regulating intracellular nitric oxide (NO) levels, the mechanism through which NO affects polysaccharide biosynthesis in Nostoc flagelliforme was explored from the perspective of S-nitrosylation (SNO). The addition of NO donor and scavenger showed that intracellular NO had a significant positive effect on the polysaccharide yield of N. flagelliforme. To explore the mechanism, we investigated the relationship between NO levels and the activity of several key enzymes involved in polysaccharide biosynthesis, including fructose 1,6-bisphosphate aldolase (FBA), glucokinase (GK), glucose 6-phosphate dehydrogenase (G6PDH), mitochondrial isocitrate dehydrogenase (ICDH), and UDP-glucose dehydrogenase (UGDH). The enzymatic activities of G6PDH, ICDH, and UGDH were shown to be significantly correlated with the shifts in intracellular NO levels. For further validation, G6PDH, ICDH, and UGDH were heterologously expressed in Escherichia coli and purified via Ni+-NAT affinity chromatography, and subjected to a biotin switch assay and western blot analysis, which revealed that UGDH and G6PDH were susceptible to SNO. Furthermore, mass spectrometry analysis of proteins treated with S-nitrosoglutathione (GSNO) identified the SNO modification sites for UGDH and G6PDH as cysteine 423 and cysteine 249, respectively. These findings suggest that NO modulates polysaccharide biosynthesis in N. flagelliforme through SNO of UGDH and G6PDH. This reveals a potential mechanism through which NO promotes polysaccharide synthesis in N. flagelliforme, while also providing a new strategy for improving the industrial production of polysaccharides.

A natural variation in OsDSK2a modulates plant growth and salt tolerance through phosphorylation by SnRK1A in rice.

Plants grow rapidly for maximal production under optimal conditions; however, they adopt a slower growth strategy to maintain survival when facing environmental stresses. As salt stress restricts crop architecture and grain yield, identifying genetic variations associated with growth and yield responses to salinity is critical for breeding optimal crop varieties. OsDSK2a is a pivotal modulator of plant growth and salt tolerance via the modulation of gibberellic acid (GA) metabolism; however, its regulation remains unclear. Here, we showed that OsDSK2a can be phosphorylated at the second amino acid (S2) to maintain its stability. The gene-edited mutant osdsk2aS2G showed decreased plant height and enhanced salt tolerance. SnRK1A modulated OsDSK2a-S2 phosphorylation and played a substantial role in GA metabolism. Genetic analysis indicated that SnRK1A functions upstream of OsDSK2a and affects plant growth and salt tolerance. Moreover, SnRK1A activity was suppressed under salt stress, resulting in decreased phosphorylation and abundance of OsDSK2a. Thus, SnRK1A preserves the stability of OsDSK2a to maintain plant growth under normal conditions, and reduces the abundance of OsDSK2a to limit growth under salt stress. Haplotype analysis using 3 K-RG data identified a natural variation in OsDSK2a-S2. The allele of OsDSK2a-G downregulates plant height and improves salt-inhibited grain yield. Thus, our findings revealed a new mechanism for OsDSK2a stability and provided a valuable target for crop breeding to overcome yield limitations under salinity stress.

Natural variation in the Tn1a promoter regulates tillering in rice.

Rice tillering is an important agronomic trait that influences plant architecture and ultimately affects yield. This can be genetically improved by mining favourable variations in genes associated with tillering. Based on a previous study on dynamic tiller number, we cloned the gene Tiller number 1a (Tn1a), which encodes a membrane-localised protein containing the C2 domain that negatively regulates tillering in rice. A 272 bp insertion/deletion at 387 bp upstream of the start codon in the Tn1a promoter confers a differential transcriptional response and results in a change in tiller number. Moreover, the TCP family transcription factors Tb2 and TCP21 repress the Tn1a promoter activity by binding to the TCP recognition site within the 272 bp indel. In addition, we identified that Tn1a may affect the intracellular K+ content by interacting with a cation-chloride cotransporter (OsCCC1), thereby affecting the expression of downstream tillering-related genes. The Tn1a+272 bp allele, associated with high tillering, might have been preferably preserved in rice varieties in potassium-poor regions during domestication. The discovery of Tn1a is of great significance for further elucidating the genetic basis of tillering characteristics in rice and provides a new and favourable allele for promoting the geographic adaptation of rice to soil potassium.

Molecular Mechanism of Adenovirus Late Protein L4-100K Chaperones the Trimerization of Hexon.

Assembly of the adenovirus capsid protein hexon depends on the assistance of the molecular chaperone L4-100K. However, the chaperone mechanisms remain unclear. In this study, we found that L4-100K was involved in the hexon translation process and could prevent hexon degradation by the proteasome in cotransfected human cells. Two nonadjacent domains, 84-133 and 656-697, at the N-terminal and C-terminal regions of human adenovirus type 5 L4-100K, respectively, were found to be crucial and cooperatively responsible for hexon trimer expression and assembly. These two chaperone-related domains were conserved in the sequence of L4-100K and in the function of hexon assembly across different adenovirus serotypes. Different degrees of cross-activity of hexon trimerization with different serotypes were detected in subgroups B, C, and D, which were proven to be controlled by the interaction between the C-terminal chaperone-related domain of L4-100K and hypervariable regions (HVR) of hexon. Additionally, HVR-chimeric hexon mutants were successfully assembled with the assistance of the 1-697 mutant. Structural analysis of 656-697 by nuclear magnetic resonance and structural prediction of L4-100K using Robetta showed that the two conserved domains are mainly composed of α-helices and are located on the surface of the highly folded core region. Our research provides a more complete understanding of hexon assembly and guidance for the development of hexon-chimeric adenovirus vectors that will be safer, smarter, and more efficient. IMPORTANCE Adenovirus vectors have been widely used in clinical trials of vaccines and gene therapy, although some deficiencies remain. Chimeric modification of the hexon was expected to improve the potency of preexisting immune evasion and targeting, but in many cases, viral packaging is prevented by the inability of the chimeric hexon to assemble correctly. So far, few studies have examined the mechanisms of hexon trimer assembly. Here, we show how the chaperone protein L4-100K contributes to the assembly of the adenovirus capsid protein hexon, and these data will provide a guide for novel adenovirus vector design and development, as we desired.

Is RNA editing truly absent in the complex thalloid liverworts (Marchantiopsida)? Evidence of extensive RNA editing from Cyathodium cavernarum.

RNA editing is a crucial modification in plants' organellar transcripts that converts cytidine to uridine (C-to-U; and sometimes uridine to cytidine) in RNA molecules. This post-transcriptional process is controlled by the PLS-class protein with a DYW domain, which belongs to the pentatricopeptide repeat (PPR) protein family. RNA editing is widespread in land plants; however, complex thalloid liverworts (Marchantiopsida) are the only group reported to lack both RNA editing and DYW-PPR protein. The liverwort Cyathodium cavernarum (Marchantiopsida, Cyathodiaceae), typically found in cave habitats, was newly found to have 129 C-to-U RNA editing sites in its chloroplast and 172 sites in its mitochondria. The Cyathodium genus, specifically C. cavernarum, has a large number of PPR editing factor genes, including 251 DYW-type PPR proteins. These DYW-type PPR proteins may be responsible for C-to-U RNA editing in C. cavernarum. Cyathodium cavernarum possesses both PPR DYW proteins and RNA editing. Our analysis suggests that the remarkable RNA editing capability of C. cavernarum may have been acquired alongside the emergence of DYW-type PPR editing factors. These findings provide insight into the evolutionary pattern of RNA editing in land plants.